8-28933642-G-A

Position:

• chr8-28933642-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135726.3(HMBOX1):​c.-57-30169G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 151,972 control chromosomes in the GnomAD database, including 31,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31300 hom., cov: 31)
• Consequence: HMBOX1 NM_001135726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

Genes affected

HMBOX1 (HGNC:26137): (homeobox containing 1) Enables double-stranded telomeric DNA binding activity; identical protein binding activity; and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II; positive regulation of telomerase activity; and positive regulation of telomere maintenance via telomerase. Located in several cellular components, including centrosome; chromosome, telomeric region; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMBOX1	NM_001135726.3	c.-57-30169G>A		intron_variant		ENST00000287701.15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMBOX1	ENST00000287701.15	c.-57-30169G>A		intron_variant		1	NM_001135726.3	P4

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97164 AN: 151854 Hom.: 31276 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.640 AC: 97238 AN: 151972 Hom.: 31300 Cov.: 31 AF XY: 0.642 AC XY: 47688 AN XY: 74296

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.637

Alfa AF: 0.650 Hom.: 31267

Bravo AF: 0.646

Asia WGS AF: 0.660 AC: 2289 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2221894; hg19: chr8-28791159;